Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
-
J. Cereb. Blood Flow Metab. · Nov 2016
Robust effects of genetic background on responses to subarachnoid hemorrhage in mice.
Outcome varies among patients with subarachnoid hemorrhage but known prognostic factors explain only a small portion of the variation in outcome. We hypothesized that individual genetic variations influence brain and vascular responses to subarachnoid hemorrhage and investigated this using inbred strains of mice. Subarachnoid hemorrhage was induced in seven inbred and a chromosome 7 substitution strain of mouse. ⋯ Our data suggested that mouse genetic background influences outcome of subarachnoid hemorrhage. Investigations into the genetic factors causing these inter-strain differences may provide insight into the etiology of the brain damage following subarachnoid hemorrhage. These findings also have implications for animal modeling of disease and suggest that genetic differences may also modulate outcome in other cardiovascular diseases.
-
J. Cereb. Blood Flow Metab. · Nov 2016
Selective cerebral perfusion prevents abnormalities in glutamate cycling and neuronal apoptosis in a model of infant deep hypothermic circulatory arrest and reperfusion.
Deep hypothermic circulatory arrest is often required for the repair of complex congenital cardiac defects in infants. However, deep hypothermic circulatory arrest induces neuroapoptosis associated with later development of neurocognitive abnormalities. Selective cerebral perfusion theoretically provides superior neural protection possibly through modifications in cerebral substrate oxidation and closely integrated glutamate cycling. ⋯ Following 2.5 h of cerebral reperfusion, we observed similar cerebral adenosine triphosphate levels, absolute levels of lactate and citric acid cycle intermediates, and carbon-13 enrichment among three groups. However, deep hypothermic circulatory arrest induced significant abnormalities in glutamate cycling resulting in reduced glutamate/glutamine and elevated γ-aminobutyric acid/glutamate along with neuroapoptosis, which were all prevented by selective cerebral perfusion. The data suggest that selective cerebral perfusion prevents these modifications in glutamate/glutamine/γ-aminobutyric acid cycling and protects the cerebral cortex from apoptosis.